Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Preparation and quality evaluation of Eriodictyol chewable tablet / 中国药房

OBJECTIVE To prepare the Eriodictyol chewable tablet and to evaluate its quality. METHODS The chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose （MCC） and mannitol as fillers， polyvinylpyrrolidone （PVP） as adhesive， citric acid and sucralose as flavor correction agents， magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance， taste， flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test， and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance， weight difference， hardness， fragility， eriodictyol content， dissolution and content uniformity. RESULTS The optimal formulation was as follows： 26.4% eriodictyol （50 mg each piece）， 45% mannitol， 25% MCC， 0.3% citric acid， 0.3% sucralose， 1% magnesium stearate， 2% PVP （preparing 5% solution using purified water）. The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76， 8.75 and 8.80 （RSD＝0.30%， n＝3）， respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface； the average tablet weight was 192.57 mg， the average hardness was 57.36 N， the fragility was 0.09%， the average content of eriodictyol per tablet was 50.74 mg， the cumulative dissolution within 30 min was exceeding 80%， and the content uniformity was 5.51. CONCLUSIONS Eriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Optimization of on-site supervision strategy based on big data of quality risk in drug enterprises / 中国药房

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Lean methodology: contributions to improving work processes in health and nursing / Metodología Lean: aportes a la mejora de los procesos de trabajo en salud y enfermería / Metodologia Lean: contribuições para melhoria dos processos de trabalho em saúde e enfermagem

ABSTRACT Objective: to investigate the contributions of applying the Lean methodology to improve work processes in health and nursing and its impact on associated financial aspects. Method: an integrative review, carried out in six databases, whose sample of ten (100.0%) studies was analyzed and summarized descriptively. Results: the outcomes obtained were stratified into: benefits/barriers to Lean Healthcare implementation; economic aspects involving Lean Healthcare implementation; and process improvements through Lean Healthcare implementation. The majority of studies (60.0%) were carried out in university hospitals, contexts that need to continually improve the quality of services provided, generally with scarce and limited resources, which support the viability of maintaining the teaching, research and extension tripod. Conclusion: three (30.0%) studies highlighted the financial aspects associated with Lean methodology application. The others only mentioned the possibility of financial gains through improving processes and reducing waste.

RESUMEN Objetivo: investigar las contribuciones de la aplicación de la metodología Lean a la mejora de los procesos de trabajo en salud y enfermería y su impacto en los aspectos financieros asociados. Método: revisión integradora, realizada en seis bases de datos, cuya muestra de diez (100,0%) estudios fue analizada y resumida de forma descriptiva. Resultados: los resultados obtenidos se estratificaron en: beneficios/barreras para la implementación de Lean Healthcare; aspectos económicos que implican la implementación de Lean Healthcare; y mejoras de procesos mediante la implementación de Lean Healthcare. La mayoría de los estudios (60,0%) se realizaron en hospitales universitarios, contextos que necesitan mejorar continuamente la calidad de los servicios prestados, generalmente con recursos escasos y limitados, que sustentan la viabilidad de mantener el trípode de docencia, investigación y extensión. Conclusión: tres (30,0%) estudios destacaron los aspectos financieros asociados a la aplicación de la metodología Lean. Los demás solo mencionaron la posibilidad de obtener ganancias financieras mejorando los procesos y reduciendo el desperdicio.

RESUMO Objetivo: investigar as contribuições da aplicação da metodologia Lean para melhoria dos processos de trabalho em saúde e enfermagem e sua repercussão nos aspectos financeiros associados. Método: revisão integrativa, realizada em seis bases de dados, cuja amostra de dez (100,0%) estudos foi analisada e sintetizada descritivamente. Resultados: os desfechos obtidos foram estratificados em: benefícios/barreiras para implantação do Lean Healthcare; aspectos econômicos envolvendo a implantação do Lean Healthcare; e melhorias em processos por meio da implantação do Lean Healthcare. A maioria dos estudos (60,0%) foi realizada em hospitais universitários, contextos que precisam melhorar, continuamente, a qualidade dos serviços prestados, geralmente com recursos escassos e limitados, os quais sustentam a viabilidade da manutenção do tripé ensino, pesquisa e extensão. Conclusão: três (30,0%) estudos evidenciaram os aspectos financeiros associados à aplicação da metodologia Lean. Os demais apenas mencionaram a possibilidade de ganhos financeiros por meio da melhoria de processos e redução de desperdícios.

Lean and/or Six Sigma for process optimization in the perioperative period: an integrative review / Lean y/o Six Sigma para optimizar los procesos en el periodo perioperatorio: revisión integradora / Lean e/ou Six Sigma para otimização de processos no período perioperatório: revisão integrativa

ABSTRACT Objective: To analyze the evidence on the influence of Lean and/or Six Sigma for process optimization in the perioperative period. Methods: Integrative review carried out in the MEDLINE (PubMed), Web of Science, EMBASE, CINAHL, Scopus and LILACS databases on the use of Lean and/or Six Sigma to optimize perioperative processes. The studies included were analyzed in three thematic categories: flow of surgical patients, work process and length of stay. Results: The final sample consisted of ten studies, which covered all operative periods. Lean and/or Six Sigma make a significant contribution to optimizing perioperative processes. Final considerations: Lean and/or Six Sigma optimize perioperative processes to maximize the achievement of system stability indicators, making it possible to identify potential problems in order to recognize them and propose solutions that can enable the institution of patient-centered care.

RESUMEN Objetivo: Analizar las evidencias sobre la influencia del Lean y/o Six Sigma para optimizar los procesos en el periodo perioperatorio. Métodos: Es una revisión integradora llevada a cabo en las bases de datos MEDLINE/PubMed, Web of Science, EMBASE, CINAHL, Scopus y LILACS, sobre la utilización del Lean y/o Six Sigma para optimizar los procesos en el perioperatorio. Los estudios incluidos se analizaron en tres categorías temáticas: flujo de pacientes quirúrgicos, proceso de trabajo y tiempo de la estancia. Resultados: La muestra final estuvo formada por diez estudios, los cuales contemplaron todos los períodos operatorios. Lean y/o Six Sigma contribuyen grandemente para mejorar los procesos en el perioperatorio. Consideraciones finales: Lean y/o Six Sigma optimizan los procesos perioperatorios al maximizar el alcance de los indicadores de estabilidad de los sistemas, facilitando la identificación de problemas potenciales para reconocer y proponer soluciones que ayuden a instituir un cuidado más centrado en el paciente.

RESUMO Objetivo: Analisar as evidências acerca da influência do Lean e/ou Six Sigma para otimização de processos no período perioperatório. Métodos: Revisão Integrativa realizada nas bases de dados MEDLINE (PubMed), Web of Science, EMBASE, CINAHL, Scopus e LILACS, a respeito do uso do Lean e/ou Six Sigma para otimização de processos no perioperatório. Os estudos incluídos foram analisados em três categorias temáticas: fluxo de pacientes cirúrgicos, processo de trabalho e tempo de permanência. Resultados: A amostra final foi composta por dez estudos, os quais contemplaram todos os períodos operatórios. Lean e/ou Six Sigma contribuem de forma expressiva para a otimização dos processos no perioperatório. Considerações finais: Lean e/ou Six Sigma otimizam processos perioperatórios em vista da maximização do alcance de indicadores de estabilidade dos sistemas, tornando possível a identificação de potenciais problemas para o reconhecimento e proposição de soluções que possam viabilizar a instituição de um cuidado centrado no paciente.

Niveles de referencia diagnósticos en equipos de radiografía dental en Bogotá, Colombia

Introducción: Las radiografías dentales son una de las exposiciones médicas más frecuentes a la radiación ionizante. El uso de radiación ionizante está asociado a un riesgo probable de desencadenar efectos biológicos adversos y posibles daños a la salud del paciente. Para evitar que los pacientes reciban dosis innecesariamente altas durante estas exposiciones, la Comisión Internacional de Protección Radiológica recomienda la utilización de los niveles de referencia para diagnóstico, como una herramienta efectiva de ayuda a la optimización de la protección radiológica de los pacientes. Objetivo: Estimar los niveles de referencia para diagnóstico en radiografía dental intraoral y panorámica en la ciudad de Bogotá, D. C. Metodología: Se evaluaron los parámetros de exposición radiográficos de los equipos y la calidad de imagen en 68 equipos de radiografía dental periapical y 23 equipos de radiografía panorámica. Se estimaron las magnitudes dosimétricas de kerma incidente en aire (Kai) en equipos intraorales para la radiografía de un maxilar molar de un adulto y el producto kerma aire-área (PKA) en equipos de radiografía panorámica en un examen de un adulto estándar. Resultados: El tercer cuartil de la distribución de kerma incidente en aire para radiografía intraoral fue de 3,3 mGy y del producto kerma aire-área para radiografía panorámica fue de 103,9 mGycm2. En la distribución de frecuencias de kerma incidente en aire para radiografía intraoral, el porcentaje más alto de equipos estuvo en el rango de 2,0-3,0 mGy. En la distribución de frecuencias del producto kerma aire-área para los equipos de radiografía panorámica, el porcentaje más alto de equipos estuvo en el rango de 60 a 80 mGycm2. Discusión: Las instituciones consideradas para establecer los Niveles de Referencia para Diagnóstico en este estudio contaron con una adecuada calidad de la imagen evaluada con un maniquí dental, pero las variaciones en las dosis de radiación entre instituciones señalan la necesidad de implementar herramientas que contribuyan a la optimización de las prácticas. Conclusiones: Se recomienda usar los valores de los niveles de referencia para diagnóstico encontrados en esta investigación para optimizar la protección radiológica en las exposiciones radiológicas dentales, y se espera que este estudio sirva de base para nuevas investigaciones en las demás ciudades del país.

Introduction: Dental X-rays are one of the most frequent medical exposures to ionizing radiation. The use of ionizing radiation is associated with a probable risk of triggering adverse biological effects and possible damage to the patient's health. To prevent patients from receiving unnecessarily high doses during these exposures, the International Commission on Radiological Protection recommends the use of diagnostic reference levels as an effective tool to help optimize radiological protection for patients. Objective: To estimate diagnostic reference levels in intraoral and panoramic dental radiography in the city of Bogotá, D.C. Methodology: In 68 periapical dental radiography equipment and 23 panoramic radiography equipment, the radiographic exposure parameters of the equipment and image quality were evaluated. The dosimetric magnitudes of incident air kerma (Ka,i) in intraoral equipment for the radiography of a maxillary molar of an adult and the air kerma-area product (PKA) in panoramic radiography equipment in a standard adult examination were estimated. Results: The third quartile of the incident air kerma distribution for intraoral radiography was 3,3 mGy and the air kerma-area product for panoramic radiography was 103,9 mGycm2. In the frequency distribution of incident air kerma for intraoral radiography, the highest percentage of equipment was in the range of 2,0-3,0 mGy, and in the frequency distribution of the air kerma-area product for equipment of panoramic radiography, the highest percentage of the equipment was in the range of 60 to 80 mGy cm2. Discussion: The institutions considered to establish the diagnostic reference levels in this study had an adequate quality of the image evaluated with a dental phantom, but the variations in radiation doses between institutions indicate the need to implement tools that contribute to the optimization of the practices. Conclusions: It is recommended to use the values of the diagnostic reference levels found in this research to optimize radiological protection in dental radiological exposures, and it is expected that this study will serve as a basis for further research in other cities of the country.

Optimization Method of Whole Wheat Flour, Soybean Flour, Oyster Meat Powder for Nutrient- Dense Composite Flour

Aim: To study the production of Nutrient – Dense Composite Flour from the blends of whole wheat flour, soybean flour (full fat) and oyster meat powder. Study Design: The study was design using the D-optimal combination design of Response Surface Methodology (RSM). Place and Duration of Study: The study was carried out at Department of Food, Nutrition and Home Science, University of Port Harcourt (Processing of raw materials) and the Department of Food Technology, Federal Institute of industrial research Oshodi, Lagos (Analysis of raw materials) between October 2021 and August 2022. Methodology: The raw materials were each processed to have wholesome flours, and then they were combined according to the matrix generated, which had ranges of 70 – 100%, 0 – 22%, and 0 – 8% for whole wheat flour (WWF), soybean flour (SBF) and oyster meat powder (OMP) respectively. Results: The design was used to assess the significance (5% probability) of the moisture, fat, and protein content, which ranged from 8.09 to 11.37%, 1.80 to 8.52% and 9.70 to 19.07% respectively; the water absorption (72.00 - 79.10BU), dough stability (9.3 - 17.5BU) and mixing tolerance index (25 - 50BU); and lightness and yellowness, which ranged from 65.48 - 83.2 and 13.77 - 23.58 respectively, of the flour blends. Protein content, water absorption dough stability, and mixing tolerance index were prioritized while moisture content, fat content, and yellowness were minimized for the numerical optimization of the responses. This study highlights the possibilities of utilizing non-conventional raw materials in the production of composite flour with balance nutritional and baking qualities. Conclusion: The best flour combination was 72.51% whole wheat flour, 19.63% soybean flour, and 7.86% oyster meat powder.

Niveles de referencia para diagnóstico según PUBMED: ¿es suficiente la información disponible? / Diagnostic reference levels according to PUBMED: is the information available sufficient?

RESUMEN Los Niveles de Referencia para Diagnóstico (NRD) son una herramienta dinámica que gana cada vez una mayor importancia para la optimización de las exposiciones médicas. La disponibilidad de información científica es esencial en este proceso de optimización para Medicina Nuclear (MN) y Radiología Diagnóstica (RD). Este trabajo presenta un estudio de la disponibilidad de información sobre los NRD para MN y RD en la base PubMed, en los últimos 20 años, empleando diferentes palabras clave. Se analizó de forma crítica la información disponible, buscando los cambios principales que se han producido como tendencia en diferentes aspectos del establecimiento de los NRD. Se verificó un desbalance significativo en la disponibilidad de literatura científica en estas dos áreas, aunque se ha incrementado la información para equipos híbridos y de forma general para todas las tecnologías. Este desbalance se hace mayor para estudios de medicina nuclear en pediatría. Se observaron avances en la forma de recolectar datos, la manera de organizar la información y analizarla, en especial con la disponibilidad de sistemas de monitoreo de dosis. Se encontró que, en los estudios TC e intervencionismo, las agrupaciones por localización anatómica están siendo acotadas o restringidas, por indicaciones clínicas que tienen similitudes en los requisitos de calidad de imagen para el diagnóstico adecuado. Similarmente en MN se vislumbra la incorporación de la actividad por peso como NRD en las tecnologías híbridas y estudios pediátricos. Este estudio demuestra que, en general, la literatura científica disponible sobre los NRD es mucho más amplia para pacientes adultos. Se requiere más estudios pediátricos, especialmente en el área de MN

ABSTRACT Diagnostic Reference Levels (DRLs) are a dynamic tool that is gaining more and more importance for the optimization of medical exposures. The availability of scientific information is essential in this optimization process for Nuclear Medicine (NM) and Diagnostic Radiology (DR). This work presents a revision of the information's availability about DRL in the PubMed database, in the last 20 years, using different search combinations. The available information was critically analyzed, looking for the main changes that have occurred as a trend in different aspects of the establishment of the NRD. A significant disparity in the amount of information between the two areas on the subject was verified, although there has been an increase of available scientific papers for hybrid equipment, and in general for all technologies. The disparity becomes greater for NM studies in pediatrics population. The way to collect data, the mode to organize the information and analyze it, has also undergone changes, mainly with radiation dose management systems. In CT and interventional studies, the grouping by anatomical locations is being constrained or modulated by clinical indications with analogous image quality requirements for proper diagnosis. Something similar happens in MN, where the incorporation of activity/patient's weight is envisioned as NRD for hybrid technologies and pediatric studies. In general, the study showed that, the scientific paper's availability about DRL for adult population are much wider. More pediatric studies on these subjects are needed, especially in NM

On the use of radiobiological-based optimization functions in radiotherapy treatment planning for prostate and head and neck cases on Monaco and Eclipse TPS / Sobre el uso de funciones de costo basadas en radiobiología en la planeación de tratamientos de radioterapia para casos de próstata y cabeza y cuello en los TPS Monaco y Eclipse

INTRODUCTION Radiobiological-based optimization functions for radiotherapy treatment planning involve dose-volume effects that could allow greater versatility when shaping dose distributions and DVHs than traditional dose volume (DV) criteria. Two of the most commercially available TPS (Monaco and Eclipse) already offer biological-based optimization functions, but they are not routinely used by most planners in clinical practice. Insight into the benefits of using EUD, TCP/NTCP-based cost functions in Monaco and Eclipse TPS was gained by comparing biological-based optimizations and physical-based optimizations for prostate and head and neck cases. METHODS Three prostate and three H&N cases were retrospectively optimized in Monaco and Eclipse TPS, using radiobiological-based cost functions vs DV-based cost functions. Plan comparison involved ICRU Report 83 parameters D95%, D50%, D2% and TCP for the PTV, and NTCP and RTOG tolerance doses for OARs. RESULTS Although there were differences between Monaco and Eclipse plans due to their dissimilar optimization and dose calculation algorithms as well as optimization functions, both TPS showed that radiobiological-based criteria allow versatile tailoring of the DVH with variation of only one parameter and at most two cost functions, in contrast to the use of three to four DV-based criteria to reach a similar result. CONCLUSION Despite the use of a small sample, optimization of three prostate and three head and neck cases allowed the exploration of optimization possibilities offered by two of the most commercially available TPS on two anatomically dissimilar regions. Radiobiological-based optimization efficiently drives dose distributions and DVH shaping for OARs without sacrifice of PTV coverage. Use of EUD-based cost functions should be encouraged in addition to DV cost functions to obtain the best possible plan in daily clinical practice

INTRODUCCION Las funciones de optimización basadas en radiobiología para la planificación del tratamiento de radioterapia implican efectos dosis volumen que podrían permitir una mayor versatilidad a la hora de dar forma a las distribuciones de dosis y DVH que los tradicionales criterios dosis-volumen (DV). Dos de los TPS más disponibles comercialmente (Mónaco y Eclipse) ya ofrecen productos de funciones de optimización de base biológica, pero la mayoría de los planificadores no las utilizan de forma rutinaria en la práctica clínica. El conocimiento de los beneficios del uso de las funciones de costos basadas en EUD, TCP/NTCP en Mónaco y Eclipse TPS se obtuvo comparando optimizaciones de base biológica y optimizaciones físicas para casos de próstata y cabeza y cuello. MÉTODOS Tres próstatas y tres casos de H&N en Mónaco y Eclipse TPS fueron optimizadas retrospectivamente usando funciones de costos basadas en radiobiología vs funciones de costos basadas en DV. La comparación de planes involucró los parámetros del Informe ICRU 83 D95%, D50%, D2% y TCP para el PTV, y dosis de tolerancia NTCP y RTOG para OAR. Resultados. Aunque hubo diferencias entre los planes Mónaco y Eclipse, debido a sus diferentes algoritmos de optimización y cálculo de dosis, así como funciones de optimización, ambos TPS demostraron que el criterio basado en radiobiología permiten una adaptación versátil del DVH con variación de un solo parámetro y como máximo dos funciones de costos, en contraste con el uso de tres o cuatro criterios basados en DV para alcanzar un resultado similar. CONCLUSIÓN A pesar del uso de una muestra pequeña, la optimización de tres casos de próstata y tres de cabeza y cuello permitió la exploración de las posibilidades de optimización que ofrecen dos de los TPS más disponibles comercialmente en dos regiones anatómicamente diferentes. La optimización basada en radiobiología impulsa de manera eficiente las distribuciones de dosis y la configuración de DVH para OAR sin sacrificar Cobertura de PTV. Se debe fomentar el uso de funciones de costos basadas en EUD además de las funciones de costos DV para obtener el mejor posible plan en la práctica clínica diaria

Mejoramiento de un método no comercial para la extracción de ADN de moscas de interés médico-legal

La obtención de ADN de moscas de interés médico-legal es de relevancia para una variedad de aplicaciones. Aunque existen métodos de extracción comerciales de ADN, su uso rutinario es limitado, en algunos escenarios. En este contexto, el uso de métodos no comerciales constituye una alternativa; sin embargo, su optimización es clave para mejorar el flujo de trabajo y los resultados. Este trabajo evaluó el impacto de variaciones a un método de precipitación salina sobre la concentración y la pureza del ADN recuperado. No se encontraron diferencias significativas en la concentración de ADN extraído entre los diferentes tiempos de incubación, probados durante la fase de extracción, mientras que el incremento en el volumen de etanol absoluto, en la fase de precipitación de ADN, mejoró significativamente la concentración de ADN obtenido. Las modificaciones propuestas reducen el tiempo de ejecución y la concentración de ADN obtenido comparado con el protocolo original.

Obtaining DNA from flies of medico-legal interest is relevant for a variety of applications. Although commercial extraction methods offer optimal DNA, their routine use is limited in some settings. In this context, the use of non-commercial methods constitutes an alternative in laboratories with limited resources however, its optimization is key to improving the workflow and the results. This work evaluated the impact of variations to a saline precipitation method on the concentration and purity of the recovered DNA. No significant differences were found in the concentration of extracted DNA between the different incubation times tested during the extraction phase. In contrast, the increased volume of absolute ethanol in the DNA precipitation phase significantly improved the concentration of DNA obtained. The proposed modifications reduce the runtime and DNA concentration obtained compared with the original protocol.

Cirugía en horario extendido: una visión de los actores involucrados / Extended hours surgery: a vision of the actors involved

Introducción. Las listas de espera para cirugía de alta prevalencia son producto de una limitada oferta ante una elevada demanda de jornadas quirúrgicas. Tienen un impacto sobre las condiciones médicas de los pacientes y la consulta por urgencias. Como respuesta, se han incorporado los espacios quirúrgicos adicionales en horarios no convencionales. Su creciente implementación, aunque controversial, se reconoce cada vez más como una nueva normalidad en cirugía. Hay una limitada documentación de la efectividad de la medida, debido a la complejidad e intereses de los participantes. Métodos. Se analizó desde una posición crítica y reflexiva la perspectiva de los actores involucrados en un programa de cirugía en horario extendido, estableciendo las posibles barreras y los elementos facilitadores de una política enfocada a procedimientos en horario no convencional. Asimismo, se describen posibles oportunidades de investigación en el tema. Discusión. Los programas quirúrgicos en horarios no convencionales implican un análisis de los determinantes de su factibilidad y éxito para establecer la pertinencia de su implementación. La disponibilidad de las salas de cirugía, una estandarización de los procedimientos y una cultura de seguridad institucional implementada por la normativa vigente, favorecen estas acciones operacionales. Los aspectos económicos del prestador y del asegurador inciden en la planeación y ejecución de esta modalidad de trabajo. Conclusión. La realización segura y el éxito de un programa de cirugía en horario no convencional dependen de la posibilidad de alinear los intereses de los actores participantes en el proceso

Introduction. Waiting lists for high-prevalence surgeries are the product of limited supply due to a high demand for surgical days. They have an impact on patients' medical conditions and emergency consultation. In response, additional surgical spaces have been incorporated at unconventional times. Its growing implementation, although controversial, is increasingly recognized as a new normal in surgery. There is limited documentation of the effectiveness of the measure due to the complexity and interests of the participants. Methods. The perspective of the actors involved in an extended hours surgery program was analyzed from a critical and reflective position, establishing the possible barriers, and facilitating elements of a policy focused on procedures during unconventional hours. Possible research opportunities on the topic are also described. Discussion. Surgical programs at unconventional times involve an analysis of the determinants of their feasibility and success to establish the relevance of implementation. The availability of operating rooms, a standardization of procedures and a culture of institutional security implemented by current regulations, favor these operational actions. The economic aspects of the provider and the insurer affect the planning and execution of this type of work. Conclusion. The safe realization and success of a surgical program in unconventional hours depend on the possibility of aligning the interests of the actors involved in the process

Optimization of Growth Parameters for Enhancing the Production of Biosurfactants from Pediococcus pentosaceus S-2

Numerous Lactic acid bacteria (LAB) have been found to be capable of synthesizing surface-active compounds i.e biosurfactants. These are amphiphilic compounds produced by microorganisms on their cell surface or secreted extracellularly that have a tendency to reduce surface and interfacial tension. In the present study, different process parameters including nitrogen and carbon source, pH, temperature, aeration and agitation were optimized to maximize the production of biosurfactants from Pediococcus pentosaceus S-2. Xylose (1.5%) and yeast extract (1.5%) act as better carbon and nitrogen sources respectively for the production of biosurfactants. Maximum biosurfactant yield was observed at pH 6, a temperature of 35o C, an agitation rate of 200 rpm and with inoculum size of 3%. The high yield of biosurfactants produced from Pediococcus pentosaceus S-2 by utilizing media supplemented with whey under optimized conditions.

Prueba de microneutralización para la detección de anticuerpos contra el virus dengue serotipo 2

Objetivo: Optimizar la prueba de microneutralización (MNT) para detección de anticuerpos neutralizantes contra el virus dengue serotipo 2 (DENV-2) en la línea celular Vero-76. Materiales y métodos: Se evaluaron diferentes concentraciones celulares (0.6 x105 cel/mL, 0.9 x105 cel/mL, 1.2 x105 cel/mL), porcentajes de 2 %, 3 % y 4 % de suero bovino fetal (SBF), número de pasajes del stock de virus y los días de incubación. La semilla viral se confirmó por RT-qPCR. El DENV-2 se propagó realizando 5 pasajes en células Vero-76, seguidamente se tituló el virus en placas de 96 pozos y se evaluaron 2 métodos de infección celular: monocapa y células en suspensión, además se determinó el día óptimo de coloración de las células. Obtenidos los resultados, se procesaron mediante MNT para DENV-2 las siguientes muestras: 5 sueros negativos a DENV-2 y YFV (Virus de la Fiebre Amarilla), 5 sueros negativos de anticuerpos a DENV-2 y positivos de anticuerpos a YFV y 5 sueros positivos de anticuerpos a DENV-2 seleccionados mediante la prueba de neutralización por reducción de placas (PRNT). Resultados: El método óptimo para MNT utilizó células en suspensión (0.9 x 105 cel/mL), 2 % de SBF y semilla viral pasaje 5. La mínima dilución capaz de diferenciar una muestra positiva a DENV-2 fue 1:40 y el tiempo de incubación para la MNT para DENV-2 fue de 10 días. Conclusión: La MNT con el método de células en suspensión y medio de cultivo con 2 % de SBF permite detectar anticuerpos neutralizantes IgG contra DENV-2 con resultados confiables, pudiendo analizar un mayor número de muestras con ahorro de materiales.

Objective: To optimize the microneutralization test (MNT) for the detection of neutralizing antibodies against serotype 2 of dengue fever virus (DENV-2) in a Vero-76 cell line. Materials and methods: Different cell concentrations were assessed (0.6 X 105 cells/mL, 0.9 X 105 cells/mL, and 1.2 x 105 cells/mL) with 2%, 3%, and 4% fetal bovine serum, virus stock passage number, and incubation days. Viral particles were confirmed using RT-qPCR. DENV-2 disseminated with 5 passages in Vero-76 cells, then, the virus was titrated in 96-well plaques, and two methods for cell infection were evaluated: single layer, and suspended cells. Also, the optimum day for cell staining was determined. Once results were obtained, the following samples were processed using MNT for DENV-2: five sera negative for DENV-2 and yellow fever virus (YFV), five sera negative for antibodies against DENV-2 and positive for antibodies against YFV, and five sera positive for antibodies against DENV-2 that were selected using the plate reduction neutralization test. Results: The optimum method for MNT used suspended cells (0.9 X 105 cells/mL), 2% fetal bovine serum, and viral particles at the 5th passage. The minimal dilution able to differentiate a positive sample for DENV2 was 1:40, and the MNT incubation time for DENV-2 was ten days. Conclusion: MNT with the cell suspension method and a culture medium with 2% fetal bovine serum allows the detection of IgG neutralizing antibodies against DENV-2 with reliable results, so that larger sample sizes may be assessed, saving materials to be used.

Simultaneous detection of thirteen exons of dystrophin gene by optimized multiplex PCR assay to screen Duchenne/Becker muscular dystrophy

Advancements in Polymerase Chain Reaction (PCR) technology and other techniques like Deoxyribonucleic acid (DNA)signal and target amplification have become key procedures in molecular diagnostics. PCR enables the synthesis of nucleic acids in vitro through which a DNA segment can be specifically replicated in a semiconservative way that sets forth deletion and mutation analysis. Multiplex PCR (M-PCR) is beneficial over standard and long PCR as this can amplify more than one locus using the respective primer sets. In harmony with this, the present study aimed to optimize M-PCR followed by its chemistry and condition to screen Duchenne Muscular Dystrophy (DMD) [OMIM #310200] and Becker Muscular Dystrophy (BMD) [OMIM #300376]. Muscular Dystrophies (MDs) are a broad group of hereditary, progressive, and degenerative disorders of muscles. X-linked recessive D/BMD are caused by mutation/s in the dystrophin gene [OMIM #300377] that encodes for dystrophin protein [UniProt#P11532]. As dystrophin is the human metagene with 79 exons, mutational analysis is very challenging. Chamberlain set (10 plex), Beggs set (9 Plex), and Kunkel set (7 Plex) is used for many years to diagnose this condition. However, in this study, Beggs set is customized with 13 exons to screen DMD gene mutation in a single reaction. Optimization of M-PCR was designed with many physicochemical parameters. According to the literature and after many appraisals the present study demonstrated the most sufficient concentration of various chemical components and optimal cycling conditions to optimize the modified Beggs set (13 Plex). 50 µL PCR reaction includes primer(s) (0.3–0.5 µM each), dNTP mixture (160 µM each), Dream Taq buffer (1X), Taq DNA polymerase (6U/50 µL), DNA template (250 ng/50 µL), BSA (0.4 µg/µL), and MgCl2 (1.4 mM). To get the most effective results cyclic conditions obtained were 10 min initial denaturation at 94°C, 62°C annealing temperature, and 35 PCR cycles at 72°C extending temperature. Consequently, the study successfully formulated a less expensive and simple approach for >3000 bp that was used to screen D/BMD. Finally, a developed M-PCR mix with a unique combination of specificity and sensitivity coupled with great flexibility has led to a true revolution in molecular diagnostics.

Optimización del control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2

Objetivo: Optimizar el control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2, utilizando los valores Cq de controles negativos y positivos. Material y método: Estudio prospectivo-longitudinal. La muestra estuvo constituida por 143 valores Cq para los controles negativos de alicuotado y extracción, así como para el control positivo. Se analizó la distribución normal de los valores Cq mediante la prueba de Anderson-Darling (AD) y se aplicaron pruebas de aleatoriedad. Se calculó límites de control a partir de 51 valores Cq, para luego, mediante gráficas de control, monitorizar 92 valores Cq obtenidos desde noviembre del 2020 hasta marzo del 2021. Se evaluó aceptación de lote e índices Cpk como indicadores de optimización. Los cálculos se hicieron con el programa Minitab. Resultados: Se aceptaron los lotes de valores Cq y se obtuvieron índices Cpk superiores a 1.33 para los tres tipos de control. Discusión: No existen estudios publicados que apliquen control estadístico de calidad a la detección cualitativa de SARS-CoV-2. Conclusiones: Es posible utilizar los valores Cq de los controles para optimizar el control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2, como si se tratara de una técnica de tipo cuantitativo.

Objective: To optimize the internal quality control of real-time RT-PCR for the qualitative detection of SARS-CoV-2, using the Cq values ​​of negative and positive controls. Material and method : Prospective-longitudinal study. The sample consisted of 143 Cq values for the negative aliquot and extraction controls, as well as for the positive control. The normal distribution of Cq values ​​was analyzed using the Anderson-Darling (AD) test and randomness tests were applied. Control limits were calculated from 51 Cq values, and then, using control charts, to monitor 92 Cq values ​​obtained from November 2020 to March 2021. Lot acceptance and Cpk indices were evaluated as optimization indicators. The calculations were made with the Minitab program. Results: The batches of Cq values ​​were accepted and Cpk indices higher than 1.33 were obtained for the three types of control. Discussion : There are no published studies that apply statistical quality control to the qualitative detection of SARS-CoV-2. Conclusions : It is possible to use the Cq values ​​of the controls to optimize the internal quality control of real-time RT-PCR for qualitative detection of SARS-CoV-2, as if it were a quantitative technique.

Application prospect of reaction engineering approach in studying drying behavior of single droplet during spray drying of traditional Chinese medicine / 中国中药杂志

Spray drying technology is one of the most commonly used unit operations in the production of traditional Chinese medicine(TCM) preparations, offering advantages such as short drying time and uniform product quality. However, due to the properties of TCM extracts, such as high viscosity, strong hygroscopicity, and poor flowability, there is limited scope to solve the problems of wall adhesion and clumping in spray drying from the macroscopic perspective of pharmaceutical production. Therefore, it has become a trend to study and optimize the spray drying process from the microscopic point of view by investigating single droplet evaporation behavior. Based on the reaction engineering approach(REA), the single droplet drying system, as a novel method for studying droplets, collects parameter data on individual TCM droplets during the drying process and uses the REA to process the data and establish predictive models. This approach is crucial for understanding the mechanism of TCM spray drying. This paper summarized and analyzed the cha-racteristics of various single droplet systems, the application of REA in single droplet drying systems, and its significance in optimizing the process, predicting drying states, and shortening the development cycle in the field of TCM spray drying, and looked ahead to the prospects of this method, including the introduction of new parameters and imaging techniques, aiming to provide a reference for further research in the field of TCM spray drying.

Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation / 中国中药杂志

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.

Optimization of microwave-assisted extraction of green tea polyphenols by response surface methodology / 药学实践杂志

Objective To optimize the microwave-assisted extraction process of green tea polyphenols. Methods The extraction yield of tea polyphenols was figured up by building the standard curve of gallic acid and examining the concentration of tea polyphenols in green tea extract with the introduction of a correction factor. The effects of four single factor levels of microwave extraction time, microwave output power, liquid-to-material yield, and ethanol volume fraction on the extraction yield of tea polyphenols were primarily studied in this experiment. The response surface was applied to further optimize the extraction process of green tea polyphenols after exploring the appropriate range of four single factor levels. Results The optimal extraction process was as follows: extraction time 37 s, microwave output power 350 w, material - liquid yield 1∶45 (g/ml), ethanol volume fraction 55%, and the actual extraction yield of tea polyphenols was 25.65%, which was not much different from the theoretical value. Conclusion The microwave-assisted green tea polyphenol extraction process optimized by response surface methodology is time-saving and practicable, and the extraction yield is high.

Research on mild cognitive impairment diagnosis based on Bayesian optimized long-short-term neural network model / 生物医学工程学杂志

The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.